Note: a dashed line (without arrowheads) between two compound names is meant to imply that the two names are just different instantiations of the same compound -- i.e. one may be a specific name and the other a general name, or they may both represent the same compound in different stages of a polymerization-type pathway. If an enzyme name is shown in bold, there is experimental evidence for this enzymatic activity.
Synonyms: N-acetylneuraminate catabolism, sialic acid degradation
|Superclasses:||Degradation/Utilization/Assimilation → Carboxylates Degradation|
Some taxa known to possess this pathway include : Abiotrophia defectiva , Escherichia coli K-12 substr. MG1655 , Streptococcus anginosus , Streptococcus constellatus , Streptococcus gordonii , Streptococcus intermedius , Streptococcus mitis , Streptococcus oralis , Streptococcus sanguinis
Expected Taxonomic Range:
Several viridans streptococci, such as Streptococcus oralis, are able to enter the bloodstream through dental caries and cause several serious infections, including endocarditis, brain abscesses and, in immunocompromised patients, septicaemia [Straus77, Ochiai99, Byers99].
The exact mechanisms by which these organisms proliferate in vivo are unknown. One of the potential sources of fermentable carbohydrate are host-derived sialic acids such as N-acetylneuraminate, which is present in serum, and can be liberated from glycoproteins and other sialoglyoconjugates via the action of sialidases [Beighton90, Byers00].
Several species of the viridans streptococci, including Abiotrophia defectiva, Streptococcus anginosus, Streptococcus constellatus, Streptococcus gordonii, Streptococcus intermedius, Streptococcus mitis, Streptococcus oralis and Streptococcus sanguinis are able to utilize N-acetylneuraminate as a sole carbon source, independently of sialidase production [Byers96]. The major end products of N-acetylneuraminate metabolism in these organisms are formate, acetate and ethanol.
A transport system for N-acetylneuraminate was characterized in Streptococcus oralis [Byers99]. This system followed typical Michaelis-Menten kinetics, with a Km of 21.0 μM and a Vmax of 2.65 nmoles/min/mg of dry cell mass.
The pathway for the degradation of N-acetylneuraminate has been studied in viridans streptococci, and its first part is essentially identical to the pathway found in Escherichia coli K-12 (see superpathway of N-acetylglucosamine, N-acetylmannosamine and N-acetylneuraminate degradation). The first step of the pathway consists of splitting of N-acetylneuraminate into N-acetyl-β-D-mannosamine and pyruvate, catalyzed by the enzyme N-acetylneuraminate lyase. N-acetyl-β-D-mannosamine is then phosphorylated to N-acetyl-D-mannosamine 6-phosphate. Next the acetyl group is removed (by N-acetylglucosamine-6-phosphate deacetylase), followed by removal of the ammoium group (by glucosamine-6-phosphate deaminase), resulting in formation of β-D-fructofuranose 6-phosphate, which enters glycolysis for substrate level phosphorylation.
In oral streptococci the end product of glycolysis, pyruvate, can be fermented into either (S)-lactate or to formate, acetate and ethanol. When grown on N-acetylneuraminate no lactate is produced, and only the later three products are observed [Byers96].
Subpathways: glycolysis II (from fructose 6-phosphate) , N-acetylglucosamine degradation I , N-acetylneuraminate and N-acetylmannosamine degradation , pyruvate fermentation to ethanol I , pyruvate fermentation to acetate IV , acetate formation from acetyl-CoA I
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